Growth factor binding molecules

Abstract

Growth factor binding molecules having a plurality of peptide loops attached to a non-peptide organic scaffold, preferably having pseudo-six amino acid peptide loops with four amino acid sidechains. The growth factor binding molecules specifically bind various growth factors and are suitable for treating a subject having tumors or restinosis. In one embodiment a platelet-derived growth factor binding molecule is disclosed that is used to inhibit tumor growth and angiogenesis in solid tumors.

1. A method of treating a subject suffering from, or at risk of, restenosis, comprising administering to the subject an effective amount of a growth factor binding compound 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, or a composition comprising the growth factor binding compound, wherein R is substituted or unsubstituted n-butyl, n-propyl, benzyl, (C 1 -C 12 ) alkyl, (C 7 -C 18 ) aralkyl, (C 6 -C 18 ) aryl, (C 1 -C 12 ) alkenyl, (C 7 -C 18 ) aralkenyl, or (C 1 -C 12 ) alkylether, and X are each independently cyclic peptide loops of the general structure: 
       
         
           
           
               
               
           
         
       
       wherein R 1 , R 2 , R 3 , and R 4  are each amino acid side chains that define a tetrapeptide, wherein said tetrapeptide is covalently attached at the amino and carboxy termini of said tetrapeptide to a 3-aminomethyl-5-aminobenzamide linking group, and wherein said tetrapeptide is GDFD (SEQ ID NO. 1), GDDD (SEQ ID NO. 2), D-ADGD (SEQ ID NO. 3), GDLD (SEQ ID NO. 4), GDAD (SEQ ID NO. 5), GDGY (SEQ ID NO. 6), ADGD (SEQ ID NO. 7), GDSD (SEQ ID NO. 8), GKGF (SEQ ID NO. 9), GKGK (SEQ ID NO. 10), GDND (SEQ ID NO. 11), PDGD (SEQ ID NO. 12), GDDG (SEQ ID NO. 13), or GDDY (SEQ ID NO. 14), wherein the compound inhibits, prevents or ameliorates restenosis. 
     
     
       2. The method according to  claim 1 , wherein the restenosis results from balloon angioplasty, insertion of a vascular stent, or resection of a blood vessel in the subject. 
     
     
       3. The method according to  claim 1 , wherein the subject is human. 
     
     
       4. The method according to  claim 1 , wherein the growth factor binding compound is administered to the subject with or in a pharmaceutically acceptable carrier. 
     
     
       5. The method of  claim 1 , wherein said tetrapeptide is GDFD (SEQ ID NO. 1). 
     
     
       6. The method of  claim 1 , wherein said tetrapeptide is GDDD (SEQ ID NO. 2). 
     
     
       7. The method of  claim 1 , wherein said tetrapeptide is D-ADGD (SEQ ID NO. 3). 
     
     
       8. The method of  claim 1 , wherein said tetrapeptide is GDLD (SEQ ID NO. 4). 
     
     
       9. The method of  claim 1 , wherein said tetrapeptide is GDAD (SEQ ID NO. 5). 
     
     
       10. The method of  claim 1 , wherein said tetrapeptide is GDGY (SEQ ID NO. 6). 
     
     
       11. The method of  claim 1 , wherein said tetrapeptide is ADGD (SEQ ID NO. 7). 
     
     
       12. The method of  claim 1 , wherein said tetrapeptide is GDSD (SEQ ID NO. 8). 
     
     
       13. The method of  claim 1 , wherein said tetrapeptide is GKGF (SEQ ID NO. 9). 
     
     
       14. The method of  claim 1 , wherein said tetrapeptide is GKGK (SEQ ID NO. 10). 
     
     
       15. The method of  claim 1 , wherein said tetrapeptide is GDND (SEQ ID NO. 11). 
     
     
       16. The method of  claim 1 , wherein said tetrapeptide is PDGD (SEQ ID NO. 12). 
     
     
       17. The method of  claim 1 , wherein said tetrapeptide is GDDG (SEQ ID NO. 13). 
     
     
       18. The method of  claim 1 , wherein said tetrapeptide is GDDY (SEQ ID NO. 14).